As reported in The Lancet by Menon et al, long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) showed that reductions in the diagnosis of stage III or IV ovarian cancer with annual multimodal screening compared with no screening did not translate into a mortality benefit.
Study Details
In the trial, 202,562 evaluable women from sites in England, Wales, and Northern Ireland were randomly assigned 1:1:2 between April 2001 and September 2005 to undergo annual multimodal screening (n = 50,625), annual transvaginal ultrasound screening (n = 50,623) or no screening (n = 101,314). Exclusion criteria included bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. Annual screening ended in December 2011.
The outcomes review committee was blinded to randomization group. The primary outcome was death due to ovarian or tubal cancer (revised World Health Organization 2014 definition) by June 30, 2020. Analyses were by intention to screen, comparing multimodal screening (primary analysis) and transvaginal ultrasound screening separately vs no screening.
The reduction in stage III or IV disease incidence in the multimodal screening group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended.— Menon et al
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Key Findings
At a median follow-up of 16.3 years (interquartile range [IQR] = 15.1–17.3 years), 2,055 women were diagnosed with tubal or ovarian cancer, including 522 (1.0%) in the multimodal screening group, 517 (1.0%) in the transvaginal ultrasound screening group, and 1,016 (1.0%) in the no screening group.
At 9.5 years after the end of screening, compared with the no screening group, the multimodal screening group had a 47.2% higher incidence of stage I disease, a 15.9% higher incidence of stage II disease (39.2% higher for stage I and II combined), a 4.4% lower incidence of stage III disease, and a 24.5% lower incidence of stage IV disease (10.2% lower for stage III and IV combined).
Compared with no screening, the transvaginal ultrasound screening group had increases of 17.0% and 1.1% in incidence of stage I and II disease and increases of 1.7% and 3.4% in incidence of stage III and IV disease.
A total of 1,206 women died from disease, including 296 (0.6%) in the multimodal screening group (P = .58 vs no screening), 291 (0.6%) in the transvaginal ultrasound screening group (P = .36) vs no screening, and 619 (0.6%) in the no screening group. A Cox model estimated a hazard ratio of 0.96 (95% confidence interval [CI] = 0.83–1.10) for multimodal screening and 0.94 (95% CI = 0.82–1.08) for transvaginal ultrasound screening vs no screening. A Cox model using only data from 2015 onward estimated a hazard ratio of 1.05 (95% CI = 0.86–1.30) for multimodal screening and 0.99 (95% CI = 0.80–1.22) for transvaginal ultrasound screening vs no screening.
The investigators concluded, “The reduction in stage III or IV disease incidence in the multimodal screening group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended.”
Usha Menon, FRCOG, of the MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the National Institute for Health Research, Cancer Research UK, and The Eve Appeal. For full disclosures of the study authors, visit thelancet.com.
